Down-regulation of miR-605 promotes the proliferation and invasion of prostate cancer cells by up-regulating EN2

Life Sci. 2017 Dec 1:190:7-14. doi: 10.1016/j.lfs.2017.09.028. Epub 2017 Sep 21.

Abstract

Aims: MicroRNA served as inhibitor for gene expression in various cancers. This study aimed to investigate the role of miR-605 and EN2 in prostate cancer (PCa).

Materials and methods: In this research, the expression of miR-605 and EN2 protein in PCa tissues and cells were determined by qRT-PCR and western blot, respectively. The cell proliferation was measured by Cell Counting Kit-8 (CCK-8) and the tumor cell invasion assay was accomplished with transwell system. Flow cytometry was used to analyze the cell cycle. The endogenous expression of miR-605 and EN2 was modulated by recombinant plasmids and cell transfection. Dual luciferase reporter assay was performed to determine the interaction between miR-605 and EN2 in PCa cells.

Key findings: The expression of miR-605 was lower in PCa tissue and cells than that in normal tissues and cells, while the expression of EN2 was just the opposite. Down-regulation of the EN2 by siRNA inhibited the proliferation and invasion of PC3 cells, and the cell cycle was arrested in G0/G1 phase. EN2 regulated the expression of E-cadherin and Vimentin through Snail and EN2 regulated the cell cycle and cell proliferation via PI3K/AKT pathway. MiR-605 inhibited the proliferation and invasion of PCa cells through targeting EN2.

Significance: EN2 is negatively regulated by miR-605, and down-regulation of miR-605 promotes the proliferation and invasion of PCa cells by up-regulating EN2, which leads to PCa development and progression.

Keywords: EN2; PCa; PCa cells; miR-605.

MeSH terms

  • Blotting, Western
  • Cell Cycle
  • Cell Line, Tumor
  • Cell Proliferation / genetics*
  • Disease Progression
  • Down-Regulation
  • Flow Cytometry
  • Gene Expression Regulation, Neoplastic
  • Homeodomain Proteins / genetics*
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness / genetics
  • Nerve Tissue Proteins / genetics*
  • Phosphatidylinositol 3-Kinases
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology
  • Proto-Oncogene Proteins c-akt
  • RNA, Small Interfering / administration & dosage
  • Real-Time Polymerase Chain Reaction
  • Up-Regulation

Substances

  • Homeodomain Proteins
  • MIRN605 microRNA, human
  • MicroRNAs
  • Nerve Tissue Proteins
  • RNA, Small Interfering
  • engrailed 2 protein
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt